(1) Field of the Invention
The invention relates to a novel composition of matter which is a pharmaceutical suspension comprising nevirapine hemihydrate.
(2) Description of the Related Art
Nevirapine, or 11-cyclopropyl-5,11-dihydro-4-methyl-6H-dipyrido[3,2-b:2',3'-e] [1,4] diazepin-6-one, is a known agent for the treatment of infection by HIV-1 (human immunodeficiency virus, type 1), which acts through specific inhibition of HIV-1 reverse transcriptase. Its synthesis and use are described in various publications including, inter alia, U.S. Pat. No. 5,366,972; European Patent Application No. 0 429 987, U.S. patent application Ser. No. 08/515,093 U.S. Pat. No. 5,571,912 and U.S. patent application Ser. No. 08/371,622 U.S. Pat. No. 5,569,760. Viramune.RTM. tablets, a pharmaceutical comprising nevirapine in tablet form, has recently been approved by the U.S. Food and Drug Administration for use in the treatment of HIV-1 infection.
Angel et al. [Proc. 50th Annual Meeting of the Electron Microscopy Society of America, pp. 1326-1327 (1992)] have disclosed that nevirapine exists as the hemihydrate stable form and as the anhydrous metastable form. This same reference describes an attempt to make an aqueous suspension of nevirapine, suitable for pediatric use, from the anhydrous form of the compound. The attempt was unsuccessful because, when formulated in aqueous suspension, the anhydrous nevirapine slowly converted to the hemihydrate form, yielding crystals of the hemihydrate which, over time, grew so large as to adversely affect drug dissolution and pharmaceutical performance.